crossing96/oncoscreening huggingface dataset:
Evaluating patient-reported outcome measures (PROMs) for bladder cancer: a systematic review using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist.	Patient-reported outcome measures (PROMs) are important tools used to understand patient-focused outcomes from care. Various PROMs have been developed for patients with bladder cancer (BC), although the disease's heterogeneity makes selection difficult. Accurate measurement of health-related quality of life (HRQL) can only be achieved if the PROM chosen is 'fit for purpose' (i.e. psychometrically sound). Systematic reviews of psychometric properties are useful for selecting the best PROM for a specific purpose. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) developed a checklist to improve the selection of health measurement instruments as part of a review process. Our aims were to undertake a systematic review, using the COSMIN criteria, to assess the quality of studies that report the psychometric properties of PROMs used with people with BC and determine the psychometric quality of these PROMs. An electronic search of seven databases including PubMed, MEDLINE and EMBASE (PROSPERO reference CRD42016051974) was undertaken to identify English language publications, published between January 1990 and September 2017 that evaluated psychometric properties of PROMs used in BC research. Two researchers independently screened abstracts and selected full-text papers. Studies were rated on methodological quality using the COSMIN checklist. Overall, 4663 records were screened and 23 studies, reporting outcomes in 3568 patients, were evaluated using the COSMIN checklist. Most PROMs had limited information reported about their psychometric properties. Studies reporting on the Bladder Cancer Index (BCI) and Functional Assessment of Cancer Therapy Vanderbilt Cystectomy Index (FACT-VCI) provided the most detail and these PROMs could be evaluated on the most COSMIN properties. Based on the available evidence, no existing PROM stands out as the most appropriate to measure HRQL in BC populations. This is due to two factors; (i) the heterogeneity of BC and its treatments (ii) no PROM was evaluated on all COSMIN measurement properties due to a lack of validation studies. We suggest future evaluation of generic, cancer generic and BC-specific PROMs to better understand their application with BC populations and propose strategies to help clinicians and researchers.	bladder
Glaucocalyxin A induces G2/M cell cycle arrest and apoptosis through the PI3K/Akt pathway in human bladder cancer cells.	Glaucocalyxin A (GLA), a major component isolated from Rabdosia japonica, has been proven to show anti-bacterial and anti-tumor biological characteristics according to previous studies. However, its potential effect on bladder cancer remains unknown. The present research aims to investigate the underlying mechanism in treating bladder cancer in vivo and in vitro. Cell proliferation was analyzed by CCK-8 assay and colony formation. Flow cytometry was used to measure the cell cycle distribution and apoptosis. The expressions of the cell cycle and apoptosis-related proteins were detected by western blotting and immunofluorescence staining. Meanwhile, the in vivo study was performed to evaluate the anti-tumor effect on a UMUC3 subcutaneous tumor of NOD/SCID mice model. GLA suppressed colony-formation ability, triggered G2/M arrest and promoted apoptosis of UMUC3 cells in a dose-dependent manner. Furthermore, western blotting showed that GLA downregulated the expressions of PI3K p85, p-Akt, Bcl-2, CDK1, Cyclin B1 whereas upregulated the levels of PTEN, Bax, Cleaved Caspase-3. In vivo, GLA at a dosage of 20 mg/kg significantly inhibited tumor growth compared with the control group by intraperitoneal injection. These results suggested that GLA-related G2/M arrest and apoptosis in UMUC3 cells were mediated by a suppressed PI3K/Akt signaling pathway, which regulated p21(Waf1/Cip1) as well as intrinsic caspase cascade. Collectively, our observations could help to develop new drugs targeting the PI3K/Akt pathway for the treatment of bladder cancer.	bladder
Verteporfin inhibits YAP-induced bladder cancer cell growth and invasion via Hippo signaling pathway.	The highly conserved Hippo signaling pathway is one of the most important pathways involved in tumorigenesis and progress. Previous studies show that YAP, the transcriptional coactivator of Hippo pathway, is expressed highly in many clinical bladder cancer tissues and plays crucial role on bladder cancer progress. To find the YAP-specific target drug and its molecular mechanism in bladder cancer, we apply Verteporfin (VP), a YAP specific inhibitor to function as anti-bladder cancer drug and discover that VP is able to inhibit bladder cancer cell growth and invasion in a dosage dependent manner. Moreover, we demonstrate that VP may inhibit bladder cancer cell growth and invasion via repressing target genes' expression of the Hippo signaling pathway. In further study, we provide evidence that VP is able to inhibit excessive YAP induced bladder cancer cell growth and invasion. To address the repressive function of VP against YAP in bladder cancer, we check the target genes' expression and find VP can dramatically repress YAP overexpression induced Hippo pathway target genes' expression. Taken together, we discover that VP inhibits YAP-induced bladder cancer cell growth and invasion via repressing the target genes' expression of Hippo signaling pathway.	bladder
ACR Appropriateness Criteria(®) Pretreatment Staging of Muscle-Invasive Bladder Cancer.	Muscle-invasive bladder cancer (MIBC) has a tendency toward urothelial multifocality and is at risk for local and distant spread, most commonly to the lymph nodes, bone, lung, liver, and peritoneum. Pretreatment staging of MIBC should include imaging of the urothelial upper tract for synchronous lesions; imaging of the chest, abdomen, and pelvis for metastases; and MRI pelvis for local staging. CT abdomen and pelvis without and with contrast (CT urogram) is recommended to assess the urothelium and abdominopelvic organs. Pelvic MRI can improve local bladder staging accuracy. Chest imaging is also recommended with chest radiograph usually being adequate. FDG-PET/CT may be appropriate to identify nodal and metastatic disease. Chest CT may be useful in high-risk patients and those with findings on chest radiograph. Nonurogram CT and MRI of the abdomen and pelvis are usually not appropriate, and neither is radiographic intravenous urography, Tc-99m whole body bone scan, nor bladder ultrasound for pretreatment staging of MIBC. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.	bladder
Recurrence, progression and cancer-specific mortality according to stage at re-TUR in T1G3 bladder cancer patients treated with BCG: not as bad as previously thought.	PURPOSE: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG. METHODS: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model. RESULTS: During a median follow-up of 5.2 years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P < 0.001). Progression rates differed according to the pathology at re-TUR, 25.3% in T1, 14.6% in Ta and 14.2% in case of no residual tumor (P < 0.001). Similar trends were seen in both patients with and without muscle in the original TUR specimen. CONCLUSIONS: Patients with T1G3 tumors and no residual disease or Ta at re-TUR have better recurrence, progression and CSM rates than previously reported, with a CSM rate of 13.1 and a 25.3% progression rate in re-TUR T1 disease.	bladder
Androgen Receptor Signaling Reduces Radiosensitivity in Bladder Cancer.	"Although radiotherapy often with chemotherapy has been shown to offer a survival benefit comparable with that of radical cystectomy in select patients with bladder cancer, the development of radiosensitization strategies may significantly enhance its application. Notably, emerging preclinical evidence has indicated the involvement of androgen receptor (AR) signaling in urothelial cancer progression. We here assessed whether AR signals could contribute to modulating radiosensitivity in bladder cancer cells. Ionizing radiation reduced the numbers of viable cells or colonies of AR-negative lines more significantly than those of AR-positive lines. Similarly, in AR-positive cells cultured in androgen-depleted conditions, dihydrotestosterone treatment lowered the effects of irradiation. Meanwhile, an antiandrogen hydroxyflutamide enhanced them in AR-positive cells cultured in the presence of androgens. AR knockdown or hydroxyflutamide treatment also resulted in a delay in DNA double-strand break repair 4-24 hours after irradiation. We then established ""radiation-resistant"" sublines and found considerable elevation of the expression of AR as well as DNA repair genes, such as ATR, CHEK1, and PARP-1, in these sublines, compared with respective controls. Furthermore, dihydrotestosterone induced the expression of these DNA repair genes in irradiated AR-positive cells, and hydroxyflutamide antagonized the androgen effects. Finally, in a mouse xenograft model, low-dose flutamide was found to enhance the inhibitory effects of irradiation, and its tumor size was similar to that of AR knockdown line with radiation alone. These findings suggest that AR activity inversely correlates with radiosensitivity in bladder cancer. Accordingly, antiandrogenic drugs may function as sensitizers of irradiation, especially in patients with AR-positive urothelial cancer. Mol Cancer Ther; 17(7); 1566-74. ©2018 AACR."	bladder
Influence of Body Mass Index on Clinical Outcome Parameters, Complication Rate and Survival after Radical Cystectomy: Evidence from a Prospective European Multicentre Study.	"Background/Aims/Objectives: To evaluate the influence of body mass index (BMI) on complications and oncological outcomes in patients undergoing radical cystectomy (RC). METHODS: Clinical and histopathological parameters of patients have been prospectively collected within the ""PROspective MulticEnTer RadIcal Cystectomy Series 2011"". BMI was categorized as normal weight (<25 kg/m2), overweight (≥25-29.9 kg/m2) and obesity (≥30 kg/m2). The association between BMI and clinical and histopathological endpoints was examined. Ordinal logistic regression models were applied to assess the influence of BMI on complication rate and survival. RESULTS: Data of 671 patients were eligible for final analysis. Of these patients, 26% (n = 175) showed obesity. No significant association of obesity on tumour stage, grade, lymph node metastasis, blood loss, type of urinary diversion and 90-day mortality rate was found. According to the -American Society of Anesthesiologists score, local lymph node (NT) stage and operative case load patients with higher BMI had significantly higher probabilities of severe complications 30 days after RC (p = 0.037). The overall survival rate of obese patients was superior to normal weight patients (p = 0.019). CONCLUSIONS: There is no evidence of correlation between obesity and worse oncological outcomes after RC. While obesity should not be a parameter to exclude patients from cystectomy, surgical settings need to be aware of higher short-term complication risks and obese patients should be counselled -accordingly."	bladder
Molecular markers in disease detection and follow-up of patients with non-muscle invasive bladder cancer.	Diagnosis and surveillance of non-muscle invasive bladder cancer (NMIBC) is mainly based on endoscopic bladder evaluation and urine cytology. Several assays for determining additional molecular markers (urine-, tissue- or blood-based) have been developed in recent years but have not been included in clinical guidelines so far. Areas covered: This review gives an update on different molecular markers in the urine and evaluates their role in patients with NMIBC in disease detection and surveillance. Moreover, the potential of recent approaches such as DNA methylation assays, multi-panel RNA gene expression assays and cell-free DNA analysis is assessed. Expert commentary: Most studies on various molecular urine markers have mainly focused on a potential replacement of cystoscopy. New developments in high throughput technologies and urine markers may offer further advantages as they may represent a non-invasive approach for molecular characterization of the disease. This opens new options for individualized surveillance strategies and may help to choose the best therapeutic option. The implementation of these technologies in well-designed clinical trials is essential to further promote the use of urine diagnostics in the management of patients with NMIBC.	bladder
Nomogram to Assess the Survival Benefit of New Salvage Agents for Metastatic Urothelial Carcinoma in the Era of Immunotherapy.	INTRODUCTION: Optimal end points in phase 2 trials evaluating salvage therapy for metastatic urothelial carcinoma are necessary to identify promising drugs, particularly immunotherapeutics, where response and progression-free survival may be unreliable. We developed a nomogram using data from phase 2 trials of historical agents to estimate the 12-month overall survival (OS) for patients to which observed survival of nonrandomized data sets receiving immunotherapies could be compared. PATIENTS AND METHODS: Survival and data for major prognostic factors were obtained from phase 2 trials: hemoglobin, performance status, liver metastasis, treatment-free interval, and albumin. A nomogram was developed to estimate 12-month OS. Patients were randomly allotted to discovery:validation data sets in a 2:1 ratio. Calibration plots were constructed in the validation data set and data bootstrapped to assess performance. The nomogram was tested on external nonrandomized cohorts of patients receiving pemetrexed and atezolizumab. RESULTS: Data were available from 340 patients receiving sunitinib, everolimus, docetaxel + vandetanib, docetaxel + placebo, pazopanib, paclitaxel, or docetaxel. Calibration and prognostic ability were acceptable (c index = 0.634; 95% confidence interval [CI], 0.596-0.652). Observed 12-month survival for patients receiving pemetrexed (n = 127, 23.5%; 95% CI, 16.2-31.7) was similar to nomogram-predicted survival (19%; 95% CI, 16.5-21.5; P > .05), while observed results with atezolizumab (n = 403, 39.0%; 95% CI, 34.1-43.9) exceeded predicted results (24.6%; 95% CI, 23.4-25.8; P < .001). CONCLUSION: This nomogram may be a useful tool to interpret results of nonrandomized phase 2 trials of salvage therapy for metastatic urothelial carcinoma by assessing the OS contributions of drug intervention independent of prognostic variables.	bladder
[Do initial experience with an enhanced recovery program after surgery (ERAS) improve postoperative outcomes after cystectomy?].	OBJECTIVE: To estimate the feasibility and the impact of an ERAS program after radical cystectomy for bladder cancer. MATERIALS AND METHODS: This was a retrospective study comparing a historical pre ERAS group, including all the patients undergoing cystectomy for bladder cancer from January 2013 to December 2015 with a classic procedure, and an interventional ERAS group after introducing an enhanced recovery protocol before, during and after surgery, from February 2016. The principal outcome was the postoperative length of stay. Secondary outcomes mesures were impact on perioperative complication rate (Clavien classification≥3B), readmission rate, reanimation length of stay, ileus rate and adherence to the ERAS protocol. RESULTS: There were no differences between the 2 groups as far as demographics characteristics are concerned. In total, 97 patients were included, 56 in the control group, and 41 in the ERAS group. The adherence to the protocol was about 65.8%. The ERAS group had statistically significantly shorter median length of stay (D19 versus D14; P: 0.021). The major complications rate (Clavien≥3B) were about 23.2% for the control group and 12.1% for the ERAS group (P: NS). The reinsertion of nasogastric tube were higher in the control group (39.3% vs 21.9%; P: NS) and the readmission rate was about 7.1% in the control group versus 14.6% in the ERAS group (P: NS). CONCLUSION: In conclusion, introduction and application of an enhanced recovery protocol (ERAS) after cystectomy for bladder cancer allowed for better management of postoperative outcomes. It is clearly feasible in cystectomy, and improve significantly the median postoperative length of stay. Moreover, it may be effective in terms of faster return of bowel function and reduction of majors complications. LEVEL OF EVIDENCE: 4.	bladder
MKAD-21 Suppresses the Oncogenic Activity of the miR-21/PPP2R2A/ERK Molecular Network in Bladder Cancer.	Bladder cancer represents a disease associated with significant morbidity and mortality. MiR-21 has been found to have oncogenic activity in multiple cancers, including bladder cancer, whereas inhibition of its expression suppresses tumor growth. Here, we examine the molecular network regulated by miR-21 in bladder cancer and evaluate the effects of i.v. and i.p. administration of a novel miR-21 chemical inhibitor in vivo LNA miR-21 reduced the oncogenic potential of bladder cancer cells, whereas the MKAD-21 chemically modified antisense oligo against miR-21 dose-dependently blocked xenograft growth. I.v. administration of LNA miR-21 was more effective in suppressing tumor growth than was i.p. administration. Integration of computational and transcriptomic analyses in a panel of 28 bladder cancer lines revealed a 15-gene signature that correlates with miR-21 levels. Protein Phosphatase 2 Regulatory Subunit Balpha (PPP2R2A) was one of these 15 genes and was experimentally validated as a novel miR-21 direct target gene. Gene network and molecular analyses showed that PPP2R2A is a potent negative regulator of the ERK pathway activation and bladder cancer cell proliferation. Importantly, we show that PPP2R2A acts as a mediator of miR-21-induced oncogenic effects in bladder cancer. Integrative analysis of human bladder cancer tumors and a large panel of human bladder cancer cell lines revealed a novel 15-gene signature that correlates with miR-21 levels. Importantly, we provide evidence that PPP2R2A represents a new miR-21 direct target and regulator of the ERK pathway and bladder cancer cell growth. Furthermore, i.v. administration of the MKAD-21 inhibitor effectively suppressed tumor growth through regulation of the PPP2R2A-ERK network in mice. Mol Cancer Ther; 17(7); 1430-40. ©2018 AACR.	bladder
Can Renal and Bladder Ultrasound Replace Computerized Tomography Urogram in Patients Investigated for Microscopic Hematuria?	PURPOSE: Computerized tomography urogram is recommended when investigating patients with hematuria. We determined the incidence of urinary tract cancer and compared the diagnostic accuracy of computerized tomography urogram to that of renal and bladder ultrasound for identifying urinary tract cancer. MATERIALS AND METHODS: The DETECT (Detecting Bladder Cancer Using the UroMark Test) I study is a prospective observational study recruiting patients 18 years old or older following presentation with macroscopic or microscopic hematuria at a total of 40 hospitals. All patients underwent cystoscopy and upper tract imaging comprising computerized tomography urogram and/or renal and bladder ultrasound. RESULTS: A total of 3,556 patients with a median age of 68 years were recruited in this study, of whom 2,166 underwent renal and bladder ultrasound, and 1,692 underwent computerized tomography urogram in addition to cystoscopy. The incidence of bladder, renal and upper tract urothelial cancer was 11.0%, 1.4% and 0.8%, respectively, in macroscopic hematuria cases. Patients with microscopic hematuria had a 2.7%, 0.4% and 0% incidence of bladder, renal and upper tract urothelial cancer, respectively. The sensitivity and negative predictive value of renal and bladder ultrasound to detect renal cancer were 85.7% and 99.9% but they were 14.3% and 99.7%, respectively, to detect upper tract urothelial cancer. Renal and bladder ultrasound was poor at identifying renal calculi. Renal and bladder ultrasound sensitivity was lower than that of computerized tomography urogram to detect bladder cancer (each less than 85%). Cystoscopy had 98.3% specificity and 83.9% positive predictive value. CONCLUSIONS: Computerized tomography urogram can be safely replaced by renal and bladder ultrasound in patients who have microscopic hematuria. The incidence of upper tract urothelial cancer is 0.8% in patients with macroscopic hematuria and computerized tomography urogram is recommended. Patients with suspected renal calculi require noncontrast renal tract computerized tomography. Imaging cannot replace cystoscopy to diagnose bladder cancer.	bladder